PROJECT SUMMARY Hepatocellular carcinoma (HCC) is the fastest rising cause of cancer-related death in the United States. One of the major treatments used for HCC is embolization, i.e. blocking the blood vessels feeding a tumor with microbeads. Drug-eluting beads (DEBs) are frequently used for this purpose. Despite the development of DEBs, patient survival rate is only 27% at 5 years. This may be due to poor drug eluting characteristics and incomplete embolization since the beads are large compared to the size of tumor capillaries. At the same time, being typically radiolucent, those beads cannot be visualized via imaging, so it is challenging to assess their successful deployment during the procedure. Therefore, the development of biodegradable materials that can block blood vessels, have tunable drug release, as well as incorporate materials with radiopaque properties, would be advantageous. We propose a novel injectable, thermo-sensitive, radiopaque and drug-eluting hydrogel as a therapeutic platform for HCC treatment, which will completely occlude tumor blood vessels. Renally clearable gold nanoparticles (AuNP) will be used to render the gel radiopaque since they have strong X-ray attenuation, excellent biocompatibility and can eventually be excreted. In this proposed research, AuNP/drug loaded hydrogels will be synthesized and will be physically and chemically characterized. In vivo studies examining the contrast generating properties of the gel, its anti-tumor effects, its biodistribution and clearance will be performed. The results of this work will set the stage for the additional efficacy and safety studies needed prior to clinical translation.

PUBLIC HEALTH RELEVANCE Current methods for treating a common form of liver cancer (hepatocellular carcinoma) result in poor outcomes for these patients, i.e. only 27% survival after 5 years. We propose to develop a drug-loaded, thermosensitive hydrogel that can be injected into the tumor, shutting off blood flow and locally delivering drug. We anticipate that this treatment will result in improved survival for liver cancer patients.